EP1598063A1 - Synergic compositions comprising vitamins, minerals and trace elements to stimulate removal of intracellular lipids - Google Patents

Abstract

An oral synergistic composition (A) is used for reducing the accumulation of intracellular lipids. (A) contains at least two vitamins and at least two minerals or trace elements to treat excessive body weight. ACTIVITY : Anorectic. MECHANISM OF ACTION : Elimination of intracellular lipids from adipocytes.

Description

The present invention relates to the use of a synergistic composition based on vitamins, minerals and of trace elements to stimulate the elimination of lipids intracellular.

Vitamins, minerals and trace elements are essential micronutrients for proper functioning metabolism of the body. Vitamins are substances organic structures with variable chemical structures and sometimes complex, while minerals and trace elements have a mineral origin.

These micronutrients each have a specific role (constitutive, catalytic, coenzyme, prohormone) and none of them can be replaced by another for ensure the maintenance of homeostasis.

Active doses are variable. Vitamins by example are active at low dose, the proportions necessary for each of them ranging from 1 to 25 000 we take the extremes that are respectively the vitamin B12 for the weakest and vitamin C for the strongest. It is the same for trace elements.

Values chosen by different experts holding account scientific data regarding the needs nutrients, motivations and dietary habits of concerned groups (children, adolescents, adults, people elderly, athletes ... etc.) have resulted in the establishment of contributions Recommended Nutrition (DUPIN H. ABRAHAM J. GIACHETTI I. Recommended nutritional intake for the population French, Tec & Doc Lavoisier, Paris, 1999) or to establish Recommended Daily Allowance (RDA).

Despite the existence of these recommendations, a number growing epidemiological studies carried out in the countries developed tend to show more deficiencies or less marked in terms of micronutrients and population segment considered.

According to the results of three main surveys carried out on the nutritional status of the French, the percentage of the population that does not receive the recommended intakes for different categories of micronutrients is as follows (SOUCCAR T. CURTAY JP The new vitamins guide, Editions du Seuil , Paris, 1996, page 11): Vitamins, minerals and trace elements Percentage of men not receiving RDA Percentage of women not receiving RDA Average Vitamin A 11.7 to 60 8 to 50 32.43 Vitamin B1 43 to 80 69 to 80 68,00 Vitamin B2 27 to 60 24.6 to 60 42.90 Vitamin B3 49.5 49.3 49,40 Vitamin B6 67.5 to 80 90 to 92 82.38 Vitamin B9 40 to 90 50 to 90 67.50 Vitamin C 25 to 60 15 to 60 40,00 Vitamin D 90 to 98 90 to 98.6 94.15 Vitamin E 40 to 100 75 to 100 78.75 Magnesium 60 80 70,00 Calcium 20 30.0 25.00 Iron 5 55 to 90 38.75 Zinc 80 90 85,00 Total 59.56

These studies tend to show that overall, 6-7 about 10 people have a disability more or less complete with respect to at least one vitamin, a mineral or a trace element but the exact consequences of these different deficiencies are not scientifically established.

Moreover, there is no food that contains all these vital elements in sufficient quantity and in adequate proportion.

The exact and complete role of vitamins, minerals and trace elements remains unknown. Proportions between these different vital elements elsewhere never been scientifically established for a given cell function.

To date, no correlation between deficiencies in vitamins, minerals and trace elements and the problem overweight or hypercholesterolemia has been scientifically established.

In developed countries, we can also observe considerable increase in the proportion of individuals (about 40% of the population) with an overload marked weight and excess weight.

Overweight results from the accumulation of large amounts of fat by some cells of the body, the adipocytes. These cells can store large amounts of lipids inside their own cytoplasm, these are the intracellular lipids. This storage excessive is actually linked to the decrease of the capacity elimination of waste and lipids by the cells.

Many strategies have been proposed for reduce overweight, such as dieting specific foods (low calorie, protein diet ...), consumption of plant extracts to "burn the fats ", drugs to reduce the feeling of hunger (isomerids), hormonal treatments, management medicalized ... etc. These treatments cause physiological imbalances that can worsen the deficiencies in vital elements, give results temporary disturb the normal physiology of cells, cause harmful and toxic effects or induce a rebound effect more commonly referred to as the expression of "Yo-Yo phenomenon".

Paradoxically, while the heart of the problem lies in the dysfunction of adipocyte metabolism, none of these rather general action strategies interested in the very cause of overweight which is lipid accumulation at the intracellular level.

There is no treatment taking into account the decreased ability of cells to remove deposits intracellular lipids whereas it is at this level that this is the real cause of overweight.

The present invention relates to the use of a synergistic composition orally or locally to base of vitamins, minerals and trace elements for targeted stimulation of the elimination capacities of cells to decrease lipid accumulation intracellular without inducing toxicity or effects secondary.

Slimming products for local application to caffeine base have the effect of mobilizing the reserves of subcutaneous fat but do not act on the accumulation of fat in the deep tissues. They did not that a superficial action which does not make it possible to reduce overweight.

Many dietary compositions or oral pharmaceuticals use products natural or synthetic, extracts of plants known for act on overweight. These compositions combine for example the effect of diuretic plant extracts, draining, swelling in the stomach and digestive tract to reduce the feeling of hunger but these compositions have no specific effect on lipid removal intracellular. The use of active ingredients pharmacological (caffeine, ephedrine, alpha and beta agonists) orally in dietary compositions or food is prohibited or statutorily limited. Medication has a central mode of action (appetite suppressant) but have many side effects.

Finally, there are many formulations based on vitamins, minerals and trace elements. These products have either a broad action and not specific, or are intended for a particular category of the population (children, adolescents, adults, women, seniors) but there is no synergistic composition to base of vitamins, minerals and trace elements that is specifically designed to boost capacity elimination of intracellular lipids to reduce the weight without inducing toxicity.

The plaintiff discovered with astonishment that the excess weight can be decreased in a very short time without producing side effects through the use of synergistic compositions associating certain vitamins, certain minerals and trace elements that stimulate elimination of intracellular lipid stores.

A synergistic composition of vitamins, minerals and trace elements stimulating strongly and specifically elimination of intracellular lipids has never been described.

An increase in the elimination capacities of intracellular lipids thus produces a decrease in storage of fat, total body mass and overweight. In addition, the effectiveness of these vitamin, mineral and trace element compositions can be further improved when combined with extracts of plants known to act on the overload weighted orally or locally or with a diet particular food.

The accumulation of intracellular lipids has been decreased in vitro by the use of synergistic compositions combining certain vitamins, certain minerals and trace elements, at doses of between 15 and 200 percent of the Recommended Daily Allowance (RDA), more particularly 50 % of RDA.

The best results were obtained with specific associations including 4 vitamins and 4 minerals or trace elements: vitamin A, vitamin B2, vitamin B9, vitamin E, magnesium, zinc, copper and selenium (decreased 89% of intracellular lipids).

The results of a 30-day clinical study performed in subjects with a body mass index 20% higher than normal allowed to show that the use of a synergistic composition containing at least minus two vitamins among vitamin A, vitamin B2, vitamin B9, vitamin E, with at least two minerals or trace element among magnesium, zinc, copper or selenium allowed a mean decrease in body weight -2.47 kg. The use of this composition is accompanied a strong improvement in the assessment parameters of the index of well-being. The results on the weight are better than when using a low calorie diet alone. The effectiveness of this synergistic composition of vitamins, minerals and trace elements is slightly improved when used in combination with a food supplement made from plants known to act overweight or with other diets. By elsewhere, the weight of volunteers who used a synergistic composition associating vitamins, minerals and micronutrients remained stable at the end of the three month of the observation period, which was not the case subjects using a low calorie diet alone. This observation shows that using a composition synergistic additionally helps to stabilize the weight in order to prevent the rebound effect observed at the end of a diet.

This is why the present application the use of synergistic compositions containing vitamins, minerals and trace elements that allow to stimulate lipid elimination capabilities intracellular to reduce overweight combination or not with compositions containing plants known to act on overweight, with a special diet, exercise machine muscular electrostimulation.

Vitamins, minerals and trace elements entering into the constitution of these compositions can come from different origins to be associated under different galenic forms whose modes of preparation are familiar to those skilled in the art.

In this application and in what follows, the term "Composition" according to the invention is intended both for the preparations solid rather than solid (liquid, semi-liquid, viscous).

In preferential conditions of implementation of the invention, the compositions are pharmaceuticals or dietetics for one-way use oral.

In preferential conditions of implementation of the invention, such a solid composition can thus be present in powder form freeze-dried or not, instantaneous (soup), in extruded form (granules, filaments, pasta), in the form of sachets, capsules, tablets.

In preferential conditions of implementation of the invention, such a non-solid composition can thus be in the form of an oral solution or diluted solution, syrup or single-dose ampoules.

In preferential conditions of implementation of the invention, the compositions are pharmaceutical or cosmetic for use by local.

According to an advantageous embodiment, these forms Galenics are pharmaceutical release compositions immediate or prolonged allowing administration by local (cream, gel, transdermal system).

According to an advantageous embodiment, the composition to stimulate the elimination capacities intracellular lipids result from the use of agents allowing the provision of vitamins, minerals and trace elements.

In preferential conditions of implementation agents allowing a contribution of vitamins can be selected from the usual forms of synthetic or vitamins, a source or extract rich in vitamins.

In preferential conditions of implementation agents allowing a contribution of minerals and trace elements can be chosen from the forms of contribution synthetic or natural uses of minerals and trace elements, a source or extract rich in minerals or trace elements, yeasts enriched with minerals or trace elements.

Such agents are for example marketed by the QUIMDIS (France) or by the company COOPER (Cooperation French Pharmaceutical, France).

The usual dose, variable according to the composition chosen, for example, can be administered daily for a period of not less than 14 days, 30 days of preferably in doses of between 15 and 200 percent Recommended Daily Allowance (RDA) for each of these elements, especially 50% of RDAs.

By AJR, we mean the amount of micronutriment actually available for use by the organization and not the gross weight of the form of feed used.

Under preferential conditions of implementation, this composition is used to accelerate the elimination intracellular lipids, cellular detoxification so to reduce weight, act on obesity, stress, fatigue, improve fitness, sleep, disorders related to age or sexual desire.

Depending on the problem, these compositions may be associated with a medicine, food or diet low calorie, a nutritional or cosmetic product for obtain synergistic effects.

This is why the present invention object the combination of synergistic compositions to stimulate intracellular lipid removal capabilities with compositions containing known plants or agents to act on overweight.

In preferential conditions of implementation of the invention, various active ingredients are used, especially plant extracts.

By "plant extract" is meant so many plants that parts of plants, for example and preferably of whole plant and preferably dried or dehydrated, and crushed, or extracts of such plants or parts of plants obtained using at least one aqueous solvent and / or organic and in a form conventionally employed in pharmacy or dietetics, liquid or solid.

In preferential conditions of implementation plant extracts and agents known to act on the overweight be chosen from the group of extracts of plant naturally containing active ingredients stimulating thermogenesis, or containing substances cholagogues and choleretic agents capable of holding fats at the intestinal level or stimulate transit intestinal.

So, we can find in the compositions according to the invention, one or more substances capable of stimulating thermogenesis, and in particular, caffeine or an extract of plant rich in caffeine obtained for example from Guarana seeds (Paullinia cupana), an extract of Green tea (Thea sinensis), an extract of Cola nut (Cola nitida), choleretic substances and cholagogues, preferably the cynarin or an extract of Artichoke (Cynara scolymus), some spice plants, preferably Ginger (Zingiber officinalis), enzymes, preferably the bromelain or a pineapple extract (Pineapple comosus) rich in bromelain, papain or Papaya extract (Carica papaya) rich in papain, plant fibers, especially fibers fruits (lemon, grapefruit, apple), cereals, pectins, fructo-oligosaccharides, preferably inulin, chitosan, clay, preferably a clay green illite type with phyllitous structure, a clay montmorillonite, kaolinite, attapulgite, sepiolite, smectite and bentonite.

Such active ingredients or plant extracts are for example marketed by BIOSPHERE (France) GREENTECH (France) or the company COOPER company (French Pharmaceutical Cooperation, France).

These combinations can therefore be in the form lyophilized powder or not, in extruded form (granules, filaments, pasta), in the form of sachets, capsules, tablets.

These combinations can also be form of a pharmaceutical or cosmetic preparation by local, cream, gel, transdermal system.

The present invention also relates to the combination of compositions that can stimulate the abilities of elimination of intracellular lipids with a diet particular food, an exercise machine or muscular electrostimulation.

In preferential conditions of implementation special diets can be chosen among the group of low-calorie diets, diets hyperprotéinés, diets improving intestinal transit.

Under preferential conditions of implementation, exercise or electrostimulation equipment may be devices or devices work the muscles to increase the expense energy of the body.

The following examples illustrate this request. These examples of compositions to stimulate the intracellular lipid removal capabilities have been developed on the basis of the results obtained during the pharmacological studies. Some compositions then have been subjected to clinical trials.

EXAMPLE 1

Capsules, tablets and sachets of vitamins, minerals and trace elements having the formula: (in milligrams per capsule, tablet or sachet) were prepared Vitamin A (beta carotene) 24.0000 Vitamin B2 (riboflavin) 0.8000 Vitamin B9 (folic acid) 0.1000 Vitamin E (powder with 50% vitamin E) 10.0000 Magnesium (magnesium oxide) 248.7000 Zinc (zinc oxide) 9.3350 Copper (copper oxide) 1.2520 Selenium (sodium selenate) 0.0822 Excipient for capsules 330 mg qs Excipient for tablets qs 400 mg Excipient for sachets qsp 1400 mg

Dosage: 1 capsule or 1 tablet each morning with a glass of water or 1 sachet that can be mixed with a yoghurt or any other food.

EXAMPLE 2

Capsules of vitamins, minerals and trace elements associated with plant extracts have been prepared and having the formula: milligrams / capsule Vitamin A (beta carotene) 24.0000 Vitamin B2 (riboflavin) 0.8000 Vitamin B9 (folic acid) 0.1000 Vitamin E (powder with 50% vitamin E) 10.0000 Magnesium (magnesium oxide) 248.7000 Zinc (zinc oxide) 9.3350 Copper (copper oxide) 1.2520 Selenium (sodium selenate) 0.0822 Guarana extract with 25% natural caffeine 25.0000 Artichoke extract with 1% cynarin 10.0000 excipients qsp 365 mg

Dosage: 1 capsule each morning with a glass of water.

EXAMPLE 3

Vitamin, mineral and micronutrient tablets associated with plant extracts having the formula: milligrams / tablet Vitamin A (beta carotene) 24.0000 Vitamin B2 (riboflavin) 0.8000 Vitamin B9 (folic acid) 0.1000 Vitamin E (powder with 50% vitamin E) 10.0000 Magnesium (magnesium oxide) 248.7000 Zinc (zinc oxide) 9.3350 Copper (copper oxide) 1.2520 Selenium (sodium selenate) 0.0822 Kola nut extract with 25% caffeine 20.0000 Pineapple extract 10.0000 Grapefruit fibers 10.0000 excipients qs 400 mg

Dosage: 2 tablets each morning with a drink of water.

EXAMPLE 4

Pouches of vitamins, minerals and trace elements associated with plants or agents known to act on overweight have been prepared having the formula: milligrams / sachet Vitamin A (beta carotene) 24.0000 Vitamin B2 (riboflavin) 0.8000 Vitamin B9 (folic acid) 0.1000 Vitamin E (powder with 50% vitamin E) 10.0000 Magnesium (magnesium oxide) 248.7000 Zinc (zinc oxide) 9.3350 Copper (copper oxide) 1.2520 Selenium (sodium selenate) 0.0822 Chicory Inulin 100.2160 Guarana extract with 25% natural caffeine 25.0000 Artichoke extract with 1% cynarin 10.0000 Green tea extract with 3% natural caffeine 10.0000 Green clay 50.0000 Pineapple juice powder 10.0000 Tamarind 7.0000 Ginger 7.0000 Karaya eraser 6.0000 excipients qsp 1400 mg

Dosage: 1 sachet per day with a glass of water or mixed with yogurt, preferably in the morning.

EXAMPLE 5

Capsules of vitamins, minerals and trace elements having the formula: milligrams / capsule Vitamin A (beta carotene) 8.0000 Vitamin B1 (thiamine hydrochloride) 0.2350 Vitamin B2 (riboflavin) 0.2670 Vitamin B3 (nicotinamide) 3.0000 Vitamin B5 (pantothenic acid) 1.0000 Vitamin B6 (pyridoxine hydrochloride) 0.3350 Vitamin B8 (biotin) 0.0250 Vitamin B9 (folic acid) 0.0350 Vitamin B12 (Cyanocobalamin) 0.000165 Vitamin C (ascorbic acid) 20.0000 Vitamin E (powder with 50% vitamin E) 3.3350 Magnesium (magnesium oxide) 83.0000 Calcium (calcium carbonate) 333.2000 Iron (iron gluconate) 18.6400 Iodine (potassium iodide) 0.0327 Potassium (potassium chloride) 24.4900 Zinc (zinc oxide) 3.1120 Copper (copper oxide) 0.4170 Selenium (sodium selenate) 0.0274 excipients qsp 540 mg

Dosage: 3 capsules a day with a glass of water, the morning preferably.

EXAMPLE 6

Pasta containing a combination of vitamins, minerals and trace elements having the formula: Milligrams for 100 grams of pasta Vitamin A (beta carotene) 24,000 Vitamin B2 (riboflavin) 0.8000 Vitamin B9 (folic acid) 0.1000 Vitamin E (powder with 50% vitamin E) 10.0000 Magnesium (magnesium oxide) 248.7000 Zinc (zinc oxide) 9.3350 Copper (copper oxide) 1.2520 Selenium (sodium selenate) 0.0822 fresh eggs 32,000.0000 Semolina qs 100 grams

Dosage: 100 to 200 grams of pasta a day cooked in the water.

EXAMPLE 7

Combination of the synergistic composition of the example 1 with 10 g in 15 centilitres of dehydrated soup water to of cabbage, vegetables and milk proteins consume at will. This diet preparation low in carbohydrates and fat, enriched in protein and dietary fiber brings about 32 kilocalories for 10 grams of dehydrated soup.

EXAMPLE 8

Combination of the synergistic composition of the example 1 with 100 grams of protein enriched pasta to consume lunch and dinner and green vegetables at will.

EXAMPLE 9

Combination of the synergistic composition of Example 1 with sachets of 1.4 g each, based on plants known to act on overweight, corresponding to the formula: Percentage by weight Chicory Inulin 82555 Precooked soy 2,500 Wheat germ 1675 Artichoke extract titrated with 3% cynarin 0950 Guarana extract titrated with 10% caffeine 0.570 Green tea extract titrated with 3% caffeine 0.570 Pre-cooked oat 0250 Apple fibers 0100 Lithothamne 0100 yeasts 0025 Aroma 0095 excipients qsp 100%

Dosage: 1 sachet per day with a glass of water or mixed with yogurt, preferably in the morning.

EXAMPLE 10

Combination of the synergistic composition of Example 1 with a slimming gel having the formula: Percentage by weight Caffeine 2.0 Centella asiatica extract 2.0 Extract of Mimosa tenuiflora 1.5 Azadirachta indica extract 0.6 Garcinia cambogia extract 5.5 excipients qsp 100% Dosage: apply a nut of product morning and evening and penetrate by a light massage.

EXAMPLE 11

A transdermal system of 10 cm ² has been prepared which makes it possible to supply the body daily with the amounts of vitamins, minerals and trace elements indicated and corresponding to the formula: milligrams / day Vitamin A (beta carotene) 24,000 Vitamin B2 (riboflavin) 0.8000 Vitamin B9 (folic acid) 0.1000 Vitamin E (powder with 50% vitamin E) 10.0000 Magnesium (magnesium oxide) 248.7000 Zinc (zinc oxide) 9.3350 Copper (copper oxide) 1.2520 Selenium (sodium selenate) 0.0822 Excipients and transdermal adhesive system qs 500 mg

EXAMPLE 12

Combination of the composition of Example 11 with a transdermal system of 10 cm ² making it possible to bring each day to the body the indicated amounts of agents known to act on overweight and plant extracts having the formula: milligrams / day Caffeine 10.0 Guarana extract 20.0 Fucus extract 10.0 Excipients and transdermal adhesive system qs 500 mg

Another subject of the present invention is a process of preparation of the compositions described above, characterized by mixing according to known methods in themselves, the active ingredient (s) with excipients or acceptable solvents, in particular pharmaceutically or cosmetically acceptable or acceptable in the diet.

TOLERANCE STUDIES:

Acute toxicity studies in rats performed according to OECD guidelines 401 under cover quality assurance programs show that the preparations used orally presented as examples are non-toxic to dose of 5 g / kg.

Studies of cutaneous local tolerance and ocular tolerance in rabbits performed according to the method official for the assessment of superficial aggression cutaneous (Order of 11 May 1993) and the official method for evaluation of eye irritation (Order of 9 June 1992) under the guise of quality assurance show that the Locally used preparations presented as examples are non-irritating.

PHARMACOLOGICAL STUDY: Searching for agent associations able to stimulate cell elimination capabilities to decrease the accumulation of intracellular lipids.

To evaluate the effect of vitamins, minerals, and trace elements on the ability of cells to remove intracellular lipid deposits, in vitro cultures of smooth muscle cells were prepared on 1 cm diameter plastic slides. the method described by Shrivastava et al. (Meth., Clinical Exp., Pharmacol., 15, 345-350, 1993.). A monolayer culture at 50-60% confluence was obtained in 4 days. The hyperlipidemic rabbit serum was added to the culture medium, the cells were incubated at 37 ° C and 5% CO2 for 48 hours and the intracytoplasmic lipid deposits were quantified. The culture medium was then replaced by a predefined white medium containing 1% fetal calf serum but not containing vitamins, minerals and trace elements.

Desired concentrations of vitamins, minerals and trace elements were prepared in the white medium predefined by dissolving the substances tested in the medium and replacing the original culture medium with the middle containing the products to be tested.

The cytotoxicity of each vitamin, mineral or trace element has been previously determined. None of the concentrations used was cytotoxic. Concentration of product tested represented 1/100 of the daily contributions Recommended (RDA) per milliliter of culture medium.

The products tested were: vitamin A (beta carotene), vitamin B1 (thiamine hydrochloride), vitamin B2 (riboflavin), vitamin B3 or PP (nicotinamide), vitamin B5 (pantothenic acid), vitamin B6 (hydrochloride pyridoxine), vitamin B8 or H, vitamin B9 (acid folic acid), vitamin B12 (cyanocobalamin), vitamin C (acid ascorbic), vitamin E (tocopherol acetate), iron (iron gluconate), iodine (potassium iodide), potassium (potassium chloride), zinc (zinc oxide), copper (oxide copper), magnesium (magnesium oxide), calcium (calcium gluconate), selenium (sodium selenate). only the elements that showed some activity during the screening stage were selected for the following experiences.

Intracellular lipid deposits were evaluated 3 days after exposure to the products tested according to method described by Shrivastava et al. (Meth, Find, Exp. Clin. Pharmacol., 15, 345-350, 1993.). The results were expressed as a percentage of average decrease in intracellular lipid deposition compared to cultures untreated control considered to contain 100% deposit lipid.

The following results were obtained with the products tested alone (Table 1), with the combinations of two products (Table 2) and with the synergistic associations of several micronutrients (Table 3). Percent decrease in intracellular lipid deposition with products tested alone (n = 24). Element Concentration Tested in μg / ml (0.016% of RDA) Percentage of decrease in intracellular lipids Vitamin A 8.0 12.6 ± 2.3 Vitamin B1 0.23 7.7 ± 1.4 Vitamin B2 0.26 14.5 ± 3.9 Vitamin B3 3.0 2.5 ± 1.0 Vitamin B5 1.0 4.5 ± 2.1 Vitamin B6 0.335 9.9 ± 2.9 Vitamin B8 0,025 1.8 ± 0.7 Vitamin B9 0,035 17.5 ± 4.6 Vitamin B12 0.0001 8.2 ± 2.5 Vitamin C 20.0 11.2 ± 4.1 Vitamin E 3.33 21.4 ± 3.9 Magnesium 66.67 22.0 ± 5.2 Calcium 178.0 0 Iron 18.64 6.3 ± 2.7 Iodine 0.03 0 Potassium 24.49 0 Zinc 3.11 16.3 ± 4.4 Copper 0.42 24.3 ± 6.2 Selenium 0,013 24.4 ± 5.3

These results show that the products tested alone have no effect on the reduction of the accumulation of intracellular lipid waste except for vitamin A, vitamin B2, vitamin B9, vitamin E, magnesium, zinc, copper and selenium. Percent decrease in intracellular lipid deposition with combinations of two products (n = 24) Percentage of decrease in intracellular lipids Vitamin A + vitamin B2 20.2 ± 4.6 Vitamin A + Vitamin B9 26.3 ± 5.5 Vitamin A + Vitamin E 29.2 ± 6.7 Vitamin A + magnesium 26.1 ± 4.4 Vitamin A + zinc 18.3 ± 4.4 Vitamin A + copper 21.3 ± 9.1 Vitamin A + selenium 17.2 ± 6.1 Vitamin B2 + Vitamin B9 18.3 ± 2.7 Vitamin B2 + Vitamin E 20.0 ± 4.1 Vitamin B2 + magnesium 30.2 ± 8.1 Vitamin B2 + zinc 21.1 ± 6.6 Vitamin B2 + copper 23.3 ± 7.3 Vitamin B9 + Vitamin E 24.4 ± 6.6 Vitamin B9 + magnesium 18.1 ± 8.2 Vitamin B9 + zinc 18.4 ± 3.2 Vitamin B9 + copper 22.6 ± 4.9 Vitamin E + magnesium 25.9 ± 4.9 Vitamin E + zinc 26.6 ± 7.6 Vitamin E + copper 17.7 ± 2.7 Zinc + copper 16.6 ± 4.9 Zinc + magnesium 21.9 ± 7.2 Copper + magnesium 24.6 ± 6.2 Vitamin B2 + selenium 24.6 ± 2.7 Vitamin E + selenium 22.2 ± 7.8 Magnesium + selenium 23.7 ± 8.2

These results show that the combination of two vitamins, minerals or trace elements does not improve the elimination of intracellular lipids. The activity is not additive. The activity of the combination of magnesium and vitamin B2 is greater than that of the two elements taken separately. Percent decrease in intracellular lipid deposition with synergistic associations of several micronutrients (n = 24), possibly in combination with plant extracts. (vitamin A = A, vitamin B2 = B2 and so on for vitamins, the international symbols of the periodic table of elements refers to the corresponding minerals and trace element). Percentage of decrease in intracellular lipids A + B2 + B9 + E 26.4 ± 6.9 A + B2 + Mg + Zn 70.0 ± 9.3 A + B5 + B6 + B8 22.4 ± 7.6 A + Fe + I + K 15.3 ± 4.3 B9 + Fe + Mg + Zn 31.2 ± 8.4 A + B2 + Cu + Se 68.4 ± 8.8 A + B2 + Mg + Se 81.2 ± 11.4 B5 + B6 + Cu + Se cytotoxic B2 + B9 + Mg + Zn 68.8 ± 11.4 B2 + B9 + Zn + Se 77.3 ± 9.9 B2 + B9 + Mg + Se 76.3 ± 13.2 B2 + B9 + Cu + Se 80.4 ± 8.2 B2 + Mg + Cu + Se 34.9 ± 6.7 B5 + B6 + B8 + Fe + I 24.6 ± 7.2 A + B2 + Mg + Cu 76.3 ± 14. 6 B2 + B9 + E + Zn 42.6 ± 14.6 D + E + Zn + Si 52.0 ± 9.0 E + Ca + Fe + Cr 36.4 ± 8.8 A + B2 + B9 + E + Mg + Zn + Cu + Se 89.2 ± 12.6 A + B2 + B9 + Mg + Zn + Cu + Se 72.1 ± 11.6 B2 + B9 + E + Mg + Zn + Cu + Se 81.6 ± 12.0 A + E + Mg + Zn + Cu + Se 71.6 ± 9.9 A + E + Zn + Cu + Se 61.4 ± 13.0 E + Mg + Zn + Cu + Se 40.1 ± 8.8 A + B2 + Mg + Cu + caffeine (0.01%) 84.4 ± 14.6 A + B2 + Mg + Cu + Soy Phytoestrogens (10%) 83.4 ± 17.3 The results show that to eliminate intracellular lipids, it is essential to combine at least two vitamins among vitamin A, vitamin B2, vitamin B9 and at least two minerals or trace elements among magnesium, zinc, copper and selenium. The best results are obtained by combining these 8 elements. Activity decreases in the absence of any of these elements.

CLINICAL STUDY: Confirmation of results in humans

Capsules, tablets and sachets containing 50% RDA in vitamin A, B2, B9, E, magnesium, zinc, copper and selenium, have been prepared (1 capsule or 1 tablet or 1 sachet per day depending on the form used).

Adult male volunteers (approximately 35%) or female (about 65%) with a mass index 20% above normal body weight were selected to evaluate the effect of different regimes on the evolution of body weight over a period of 30 days. The weight of volunteers was also evaluated 3 months after the date of beginning of the study.

The decrease in body weight was related to improving cellular metabolic functions that facilitates the elimination of intracellular lipids and waste from the body. The effect on different parameters of well-being was evaluated using score scales ranging from 0 to 4. Five groups studied under conditions identical have been established for the study conducted by a Research Institute accredited by the Ministry of Research.

Group 1: dietary supplement of vitamins, minerals and trace elements according to Example 1.

Group 2: combination of a dietary supplement of vitamins, minerals and trace elements associated with a Herbal dietary supplement according to Example 9.

Group 3: combination of a dietary supplement of vitamins, minerals and trace elements associated with a diet containing green vegetables at will, fruits and 100 grams of high protein pasta for lunch and dinner according to Example 8.

Group 4: vegetable soup diet freeze-dried as an instant mix preparation with boiling water.

Group 5: combination of a dietary supplement of vitamins, minerals and trace elements associated with diet freeze-dried vegetable soup base in the form of instant preparation to mix with boiling water according to Example 7.

The following average results were obtained: Number of volunteers Average weight loss in 30 days Index of well-being (1 to 4) H F H F Average Group 1: 8 30 -2.22 -2.61 -2.47 3.21 Group 2: 9 18 -3.67 -3.82 -3.76 3.42 Group 3: 4 12 -2.10 -2.93 -2.62 3.11 Group 4: 7 14 -1.15 -1.30 -1.22 1.80 Group 5: 12 18 -2.20 -2.75 -2.56 2.89

These results show that the association of 50% of RDA in vitamin A, vitamin B2, vitamin B9, vitamin E, magnesium, zinc, copper and selenium, decreases weight in men and women (average of -2.47 kg in 30 days) in accelerating the elimination of intracellular lipids. A improvement of the results is obtained when the composition synergistic is combined with a dietary supplement based of plants. These results can also be improved by combination with other diets but weight reduction obtained is not always significant which shows that most of the observed weight loss is due to the synergistic composition of vitamins (A, B2, B9, E), minerals and trace elements (magnesium, zinc, copper, selenium).

Group 4 volunteers receiving only one diet based on vegetable soup have shown a decrease in very much less weight than the groups receiving the composition synergistic vitamins, minerals and trace elements.

Moreover, the weight of volunteers who used a synergistic composition combining vitamins, minerals and trace elements remained stable at the end of three months of the observation period which was not the case of subjects using a low calorie diet alone. This observation shows that using a composition synergistic additionally helps to stabilize the weight in order to prevent the rebound effect observed at the end of a diet.

In the subjects studied, the index of well-being was greatly increased with the synergistic composition of vitamins, minerals and trace elements that improves remarkably the evaluation parameters of stress, sleep, fitness and fatigue which shows that the synergistic composition of vitamin A, vitamin B2, Vitamin B9, Vitamin E, Magnesium, Zinc, Copper and Selenium has a positive effect on health in general.

Claims (9)

Use of a synergistic oral composition to reduce intracellular lipid accumulation characterized in that it comprises at least two vitamins selected from vitamin A, vitamin B2, vitamin B9, vitamin E with at least two minerals or trace elements selected from magnesium, zinc, copper and selenium to treat overweight. Use of a synergistic oral composition to reduce the accumulation of intracellular lipids characterized in that it comprises at least two vitamins with two minerals or trace elements to treat overweight. Use of a synergistic composition according to Claims 1 to 2, characterized in that it is used locally. Use of a synergistic composition according to Claims 1 to 3 in combination with a composition oral agents based on agents that stimulate the thermogenesis, have a cholagogue or choleretic effect or which are known to decrease overweight. Use of a synergistic composition according to Claims 1 to 3 in combination with a diet hypocaloric food, high protein or stimulating the intestinal transit. Use of a synergistic composition according to Claims 1 to 3 in combination with a device exercise or device muscular electrostimulation. A combination of compositions as defined in one of claims 1 to 6 as a product pharmaceutical, cosmetic, dietetic or nutritional. A combination of compositions as defined in one of claims 1 to 6 and an excipient pharmaceutically or cosmetically acceptable. A combination of compositions as defined in one of claims 1 to 6 and an excipient acceptable in the diet.